Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2- Amino Substituted Benzonaphthyridines as PDK1 Inhibitors
Abstract
The present work emphasizes the utility of 2,4-dichloro-5-
methylbenzo[h][1,6]naphthyridine as starting precursors. The
reaction of 2,4-dichloro-5-methylbenzo[h][1,6]naphthyridine
with a variety of aliphatic and aromatic amines yielded 2-amino
substituted 2,4-dichlorobenzo[h]naphthyridines. All the compounds
were examined for their in vitro anticancer activity
against six human cancer lines and docked with PDK1
inhibitors. The structure-activity relationship studies are revealed
that the compounds holding aminocarbazole moiety
and triazole amine moiety improve the activity profile. All the
structures of synthesized compounds were optimized at B3LYPD3/
6-31G(d) level in the water. Furthermore, the electronic
properties and biological reactivity of the synthesized compounds
are explored using computational techniques.